The objective of the present investigation is to relate changes in isozyme pattern, which may occur during tumor progression under the selective pressure of chemotherapeutic agents, to the development of resistance to such agents. Such a mechanism may operate in those instances where key enzymes (proteins) which mediate the effect of the agents exists in multiple molecular forms which change qualitatively during development and which have different specificities. The present theory is proposed to evidence in the literature which indicates that the key enzyme (protein) is often not deleted in resistant cells, but is replaced with an enzyme of different specificity. The proposed study will include the comparison of the properties (including specificities) of the uridine kinase isozymes and the cortisol metabolite-binding proteins in embryonic and adult tissues and in tumors sensitive and resistant to the growth-inhibitory effects of the pyrimidine analogs and cortisol, respectively.